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PubMed1994

Reduced expression of phospholipase C-delta, a signal-transducing enzyme, in rat colon neoplasms induced by methylazoxymethanol acetate.

Phospholipase C (PLC), which hydrolyzes phosphoinositides, has been implicated as a key enzyme in signal transduction. We examined the expression of an isozyme of PLC, PLC-delta, in rat colon neoplasms induced by methylazoxymethanol (MAM) acetate. Large-bowel neoplasms were observed in five of 10 rats given MAM acetate (25 mg/kg body weight, by interperitoneal injection at 6 and 7 wk of age) 40 wk after treatment. Expression of PLC-delta in the neoplasms was not detected by northern blot analysis, and a low level of expression was detected by immunoblot analysis, although PLC-delta expression was apparent in the non-neoplastic colon mucosae of MAM acetate-treated rats as well as in the colon mucosae of control rats. Furthermore, analysis by reverse transcriptase-polymerase chain reaction revealed that the ratio of the expression of PLC-delta to that of beta-actin in the neoplasms was significantly lower than the ratios in the non-neoplastic colon mucosae of carcinogen-treated and control rats (P < 0.01). However, the ornithine decarboxylase (ODC) activity in the neoplasms was significantly greater than that of the non-neoplastic and control mucosae (P < 0.001). The differences in the levels of PLC-delta expression in neoplastic and non-neoplastic tissues and the inverse correlation of PLC-delta expression with ODC activity may suggest that PLC-delta has little effect on the PLC-mediated mitogenic signaling system, at least in MAM acetate-induced colon neoplasms in rats.

Animals↗
PubMedDate not supplied

Diverticular fecalith in scleroderma simulating colonic neoplasm: report of a case.

This is a report of a patient with the CRST syndrome, a mild variant of scleroderma consisting of calcinosismraynaud's phenomenon, sclerodactyly, and telangiectasia. Typical changes of scleroderma were present in the extremities, esophagus, duodenum and colon. In addition, there was a polypoid filling defect in a colonic diverticulum due to a fecalith. The radiologic appearance at first resembled a colonic neoplasm, although its location within a diverticulum and its speckled appearance suggested the possibility of a fecalith. This was confirmed at colonoscopy, which disclosed numerous wide-mouthed diverticula, with inspissated fecal material projecting from several diverticula. In patients with scleroderma and polypoid filling defects in the colon, the possibility of a fecalith within a diverticulum should be considered. Where the radiologic study is inconclusive, colonoscopy may provide a definitive diagnosis.

Adult↗
PubMed1992

Blood group-related carbohydrate antigen expression in malignant and premalignant colonic neoplasms.

Cell surface glycoconjugates of colonic epithelial cells carry certain carbohydrate antigens related to blood group substances. During the progression to malignancy, these oligosaccharide immunodeterminants undergo specific types of alterations. In colon cancers, the blood group antigens A, B, H, and Le(b), which are normally expressed only in the proximal colon, can be re-expressed in distal colon cancers or deleted in proximal colon cancers. Also, an antigen which is incompatible with the individual's blood type can be expressed. Similar alterations occur in adenomatous polyps, but with reduced frequency. The simple form of blood group-related Le(x) and Le(y) antigens found in normal mucosa can undergo modification by oligosaccharide elongation, internal fucosylation, and sialylation into novel structures found in carcinomas as well as in adenomas with greatest malignant potential. Finally, antigens representing the first steps of glycosylation, Tn, T, sialosyl-Tn (STn), which are normally cryptic in the colon, can be unmasked due to incomplete glycosylation in adenomatous polyps and cancers. Several of these antigens, such as extended Le(x), extended Le(y), T, and sialosyl-Tn, are quite cancer-specific in that they are rarely expressed in normal mucosa or hyperplastic polyps, but preferentially occur in adenomas of greatest malignant potential. As such, these antigens might be useful as candidate intermediate endpoint biomarkers.

ABO Blood-Group System↗
PubMed1995

[Streptococcus bovis in a surgical wound and a colonic neoplasm].

The association of colorectal carcinoma and septicemia or endocarditis by Streptococcus bovis is well known. Nonetheless, other localizations of infection by Streptococcus bovis have not been associated with colorectal carcinoma. The case of association of colon neoplasm with infection by Streptococcus bovis localized in the surgical wound of resection of a prostate adenoma by the transvesical route carried out four months previously is presented. Possible intraoperative bacteremia colonizing the surgical wound due to colic compression during surgery may have been the cause. This localization of infection by Streptococcus bovis should be taken into account in screening of colorectal carcinoma.

Adenocarcinoma↗
PubMed1999

[The relationship between the histopathological atypia and expression of beta-catenin in colonic neoplasms resected by endoscopy; comparison with that of p53 protein].

Previous studies have reported predominantly nuclear localization of beta-catenin as a role for colorectal carcinogenesis. In this study, we examined the immunohistochemical expression of beta-catenin and p53 protein in 90 colonic neoplasms {33 carcinomas in adenoma (CIA), 28 high grade adenomas and 29 low grade adenomas}, resected by colonic endoscopy. Out of 33 CIAs. 28 (84.8%) cases showed predominantly nuclear localization of beta-catenin, and that was significantly higher than those of both high grade (46.4%) and low grade (13.8%) adenomas. The positiveness of p53 expression in CIAs was 51.5% (17/33), while 17.9% in high grade and 3.4% in low grade adenomas. However, there was no correlation between both protein expressions (p = 0.3472, chi 2 test). The results suggests that nuclear localization and accumulation of beta-catenin is earlier event than that of p53 mutation in adenoma-carcinoma sequence, and is useful as a marker in histopathological diagnosis for malignant conversion as well as p53.

Adenoma↗
PubMed1990

[Colonic neoplasms and skin fibromas: common determinants and their significance].

To find common factors for colonic-neoplasias and skin-tags, 157 inpatients, who consecutively had a coloscopy because of intestinal complaints, were intensively examined dermatologically. Regression-analyses showed that the number of colonic polyps were age- (p = 3 x 10(-8)) and sex-dependent (1.9 x 10(-2)) and skin-tags had no influence on the number of colonic polyps. The size of colonic polyps also showed a clear age dependency (p = 3 x 10(-8)). The number of skin-tags were dependent on weight (p = 9 x 10(-3)) and age (p = 1.3 x 10(-2)), its size on the interaction of sex and triglyceride-levels (p = 3 x 10(-8)). Discriminant-analyses identified the following factors as important: age and triglyceride-concentration to recognize a patient with colonic polyps; age, positive Haemoccult-test and number of skin-tags to recognize a patient with tubulovillous adenomas or colonic carcinomas. The essential common factor of colonic polyps and skin-tags was the age. For the recognition of a patient with colonic polyps the age was the most essential factor, skin-tags, on the contrary, were unimportant. The association between colonic polyps and skin-tags therefore was merely an effect of age.

Age Factors↗
PubMed1986

Sensitivity of the Hemoccult II slide test in detecting colonic neoplasms.

It is common clinical practice to test stools for occult blood and to rely heavily upon the result in deciding whether to investigate further. Because the accuracy of such testing has been questioned, a study was conducted to estimate the sensitivity of the Hemoccult II slide test in detecting colonic carcinoma and polyps. Patients with lesions demonstrated on barium enema roentgenography had their stools examined for occult blood. One to 2 weeks before colonoscopy, stool specimens were collected for 3 consecutive days according to the manufacturer's instructions. The sensitivity of occult blood testing was 38% for patients with benign polyps and 64% for patients with polypoid carcinomas. Thus, the authors conclude that the Hemoccult II test is not reliable as a diagnostic tool and that a negative test result does not exclude the presence of a colonic neoplasm in any patient.

Adult↗
PubMed1990

[Soft skin fibromas: study of their importance and diagnostic significance for colonic neoplasms].

The aims of this study were (a) to examine the association of skin tags and colonic polyps and (b) to identify factors influencing skin tags. Therefore, a consecutive series of 157 medical ward patients with gastrointestinal symptoms who underwent colonoscopy underwent dermatological examination. Skin tags were found in 52% of these patients regardless of sex. (a) There was a statistically significant association between skin tags and colonic polyps (P = 0.33). This association, however, was based solely on an age effect. (b) Influencing factors were weight and age for the number of skin tags and the interaction between sex and the concentration of triglycerides for their size. At any given triglyceride concentration, men had larger skin tags.

Aged↗
PubMed1988

Localization of villin, a cytoskeletal protein specific to microvilli, in human ileum and colon and in colonic neoplasms.

Villin is a cytoskeletal protein of microvilli of epithelial cell brush borders found principally in absorptive cells of the intestine and proximal renal tubule. A marker of both enterocyte differentiation and epithelial cell polarity, it has been studied mainly in experimental animals. We raised monoclonal antibodies to villin and used them to localize it in human ileum and colon and in 22 colonic neoplasms. Villin is localized in the brush border of normal ileum and in the luminal border of normal colon and is expressed with increasing staining intensity as cells migrate from crypt to surface. It was present in the luminal border in all five adenomas and in 16 of 17 adenocarcinomas studied. In addition, villin staining was observed in the cytoplasm of 10 tumors, and in the basement membrane area surrounding tumor in 10 cases. In "transitional" mucosa adjacent to carcinomas it was confined to the luminal border. Abnormal expression of villin by a significant proportion of colonic tumors suggests that it may have a role as a marker of colorectal neoplasia.

Adenocarcinoma↗
PubMed1996

Cathepsin B in the growth of colorectal cancer: suppressive effect of leupeptin on the growth of DMH-induced rat colon neoplasm.

Cathepsin B, a thiol protease, has been reported to be involved in cancer progression and metastasis. The suppressive effects of two kinds of protease inhibitors, leupeptin and dietary camostate (FOY-305), on tumorigenesis and progression in 1, 2-dimethylhydrazine (DMH)-induced rat colon neoplasm were examined in relation to tissue cathepsin B activity. Male Donryu rats were treated with leupeptin or FOY-305 during or after the administration of DMH. There were no significant differences in average tumor numbers among all DMH-treated groups. However, the percentage of small tumors was significantly higher in the group in which leupeptin was supplied during DMH administration. This trend was not recognized in the FOY-305-treated groups. The ratio of cathepsin B activity in the tumors to that in the tumor-bearing tissue (T/Tb) was significantly increased with increasing tumor size (P = 0.009). The cathepsin B activity levels in the tumor-bearing mucosa in the groups which received leupeptin or FOY-305 following DMH treatment were both significantly lower than that in the group which received neither protease inhibitor (P = 0.046 and P = 0.0067, respectively). The results obtained indicate that leupeptin may have suppressed tumor growth by lowering the tissue cathepsin B activity.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Glutathione concentrations and glutathione S-transferase activity in human colonic neoplasms.

Tissue concentrations of glutathione (GSH) and the activity of glutathione S-transferases (GST) are relevant to the inactivation of a variety of xenobiotics including carcinogens and anti-neoplastic drugs. In this study, GSH concentrations and GST activity were determined in 25 adenomatous polyps removed at colonoscopy, and in cancer and uninvolved 'normal' mucosa from 58 operative specimens containing colon cancer. We also examined the relationship between GSH concentrations, GST activity and rates of cell proliferation as assessed by flow cytometry. Concentrations of GSH were significantly higher in adenomas (P = 0.001) and cancer (P = 0.001) than in uninvolved mucosa while GST activity was significantly higher in cancer (P = 0.007). There was a positive relationship between GSH concentrations and GST activity in adenomas (P = 0.001) but not in uninvolved mucosa (P = 0.06) or cancer (P = 0.4). Concentrations of GSH and GST activity were independent of results from flow cytometry. The higher concentrations of GSH in colonic neoplasms and the raised activity of GST in cancer may contribute to their resistance to anti-neoplastic drugs.

Adenoma↗
PubMed1999

Distal colonic neoplasms predict proximal neoplasia in average-risk, asymptomatic subjects.

Flexible sigmoidoscopy has been recommended as a screening method to reduce the incidence of colorectal cancer in asymptomatic, average-risk subjects through the early detection and removal of polyps. However, the association between distal and proximal colonic neoplasia and, hence, the requirement for colonoscopic follow up of screen-detected distal neoplasms is unclear. Our aims were: (i) to evaluate the risk of having proximal neoplasms in those with distal colonic neoplasms; and (ii) to determine whether the risk was dependent on the number, size, histology or morphology of the distal lesions. We prospectively evaluated asymptomatic subjects in a flexible sigmoidoscopy based screening programme. Those with rectosigmoid neoplasia underwent colonoscopy. The number, size, histology and morphology of the polyps were recorded. Advanced lesions were defined as adenomas > 1 cm or with a villous component or severe dysplasia, carcinoma in situ or cancer. Adenomatous polyps were found in 17% (135) of screening flexible sigmoidoscopies. At colonoscopy, up to 30% of subjects with distal colonic neoplasms had synchronous proximal lesions at colonoscopy and up to 20% had advanced proximal lesions. The risk of proximal colonic neoplasia was increased in those with distal sessile colonic neoplasms but appeared independent of distal lesion size, number or morphology. In conclusion, distal colonic neoplasia predicts proximal neoplasia in up to 30% of subjects and these were advanced lesions in up to 20%. We recommend that all subjects with biopsy proven distal colonic neoplasia undergo colonoscopy.

Adenoma↗
PubMed1990

Proliferation rate of colonic mucosa in normal subjects and patients with colonic neoplasms: a refined immunohistochemical method.

An increased colonic epithelial proliferation rate and an increase of the cryptal proliferative zone are probable markers of increased susceptibility to colonic cancer. In this study an immunohistochemical method using 5-bromo-deoxyuridine (BrdUrd) to measure the proliferation rate of colonic mucosa in vitro was used. Fresh endoscopic colonic biopsy specimens were incubated with BrdUrd and then processed for immunohistochemistry using a monoclonal antibody. Essential procedures with respect to the equal distribution of nuclei stained with BrdUrd in the biopsy specimens proved to be the cutting of the specimens before incubation and the use of a microwave oven at the beginning of incubation. The use of the procedure of the running average showed that 12 length cut crypts are sufficient to determine reliably the proliferation rate, expressed as the labelling index (LI). This was determined in the biopsy specimens of 10 subjects without organic colonic disease, eight patients with adenomatous colonic polyps, and in six patients with (recent) colonic carcinoma. Mean LI in the controls was significantly lower than in patients with colonic polyps and in those with colon cancer. It is concluded that this method is promising for screening persons at risk for colon cancer and will be of great potential in performing dietary intervention studies in these subjects.

Adolescent↗
PubMed1978

The cytochemical demonstration of beta-glucuronidase in colon neoplasms of rats exposed to azoxymethane.

Colon tumors induced with azoxymethane in male Fischer rats were cytochemically analyzed for beta-glucuronidase using naphthol AS-B1 glucuronide (6-bromo-2-hydroxy-3-naphthoyl-O-anisidine) as a substrate and hexazonium pararosanin as a diazo reagent. This method effectively localizes the bulk of beta-glucuronidase in the surface epithelium, the lamina propria and in the endothelial cells of the lymphoid sinuses and postcapillary venules. Polypoid lesions, adenocarcinomas and mucinous adenocarcinomas show no difference in the amount or in the localization of beta-glucuronidase; however, mucinous adenocarcinomas show a slight increase in the amount of beta-glucuronidase. The few tumors that did metastasize to lymph nodes did not show any difference in their enzyme patterns. Intestinal crypts that show a change in size and shape have a definite increase in beta-glucuronidase activity. An increase in the activity of this enzyme can also be seen in well defined neoplasms as opposed to normal areas of the colon.

Adenocarcinoma↗
PubMed1983

Comparative studies of mononuclear phagocyte function in patients with Crohn's disease and colon neoplasms.

Phagocytosis and cellular cytotoxicity by mononuclear phagocytes of blood and intestinal mucosa were studied in patients with Crohn's disease and large bowel neoplasms. Antibody coated sheep erythrocytes were used for phagocytic assays and cellular cytotoxicity in vitro was measured by 24 hour isotope release from 75Selenium methionine-labelled RPMI 4788 human cancer cell cultures in the presence of mononuclear phagocyte-enriched effector populations. The mean percent of mononuclear phagocytes in Ficoll-Hypaque purified mononuclear cell suspensions of blood of healthy controls was 25.9 compared with 44.6 in patients with Crohn's disease, 45.6 in patients with colon neoplasms and 11.6 in intestinal mucosa. Phagocytic indices were similar in all groups, but the phagocytic capacity of mucosal macrophages was twice that of blood monocytes. Mean cytotoxicity of monocytes of patients with Crohn's disease was 12.8% compared with 22.9% for monocytes from normal controls, and 29.4% for patients with colon tumours. Mean cytotoxicity by mucosal macrophages was 18.0% compared with 13.2% by mucosal lymphocyte populations. Exposure of monocytes of Crohn's disease patients to bacterial lipopolysaccharide modestly increased cytotoxicity, but exposure did not alter phagocytosis by monocytes of patients or controls. The results indicate that monocytes of patients with Crohn's disease exhibit subnormal in vitro cytotoxicity. Mucosal macrophages from patients with various diseases show enhanced phagocytosis compared with blood monocytes, and they can mediate cellular cytotoxicity in vitro.

Adult↗
PubMedDate not supplied

Are hyperplastic rectosigmoid polyps associated with an increased risk of proximal colonic neoplasms?

Diminutive polyps are frequent findings on screening flexible sigmoidoscopy. To determine the significance of distal diminutive polyps, we conducted a prospective study of 162 asymptomatic, average-risk subjects who were 50 years of age or older. Subjects were divided into four groups: 42 control subjects with no polyps in the rectosigmoid, 66 subjects with at least one diminutive adenoma in the rectosigmoid, 12 subjects with a mixed hyperplastic-adenomatous polyp in the rectosigmoid, and 42 subjects with only hyperplastic polyps in the rectosigmoid. Total colonoscopy was performed on all subjects. The prevalence of proximal adenomas was 42% in the adenoma group, 25% in the mixed group, 14% in the hyperplastic group and 12% in the control group. The prevalence of proximal adenomas was significantly higher (p = 0.006) in the adenoma group as compared with the control and hyperplastic groups. Increasing age was associated with an increased prevalence of proximal adenomas. Nearly two thirds of those over 65 years of age with distal diminutive adenomas had proximal colonic neoplasms. These results indicate that diminutive rectosigmoid adenomas are good markers for proximal neoplasms. Rectosigmoid hyperplastic polyps are not associated with an increased prevalence of proximal neoplasms. Total colonoscopy is not indicated if hyperplastic polyps are the only finding on flexible sigmoidoscopy.

Aged↗